Otitis media (OM) is one of the most prevalent diseases in children and cost the US healthcare system an estimated $5 billion dollars annually. Although the primary etiology responsible for the persistence of OM conditions is a dysfunctional Eustachian tube (ET), standard treatment therapies for OM do not address the underlying biomechanical and structural abnormalities responsible for ET dysfunction. Recently, several clinical therapies which target specific mechanical and/or physical properties have been suggested to improve ET function. However, the relative effectiveness of these therapies in patient populations with different structural pathologies is not known. Therefore, the goal of this research program is to develop an in- depth understanding of how various biomechanical and biophysical properties influence ET function in different OM prone patient populations. Due to the large number of physical properties, and the complex interactions among these properties, we will elucidate the mechanisms responsible for ET dysfunction using a sophisticated multi-scale computational approach. First, established computational modeling techniques will be used to investigate how the pathological anatomy of ET tissues influences opening phenomena in various OM prone populations. Second, fluid-structure interactions and multi-scale phenomena will be incorporated into the tissue deformation models in order to investigate how various clinically relevant properties (i.e. surface tension and mucosal adhesion forces) influence ET opening. Several sensitivity analyses will be performed to identify which biomechanical or biophysical properties have the greatest impact on ET function in different patient populations. In addition, the computational models will be used to estimate changes in ET function during various pathological conditions. As a result, this research will identify the biomechanical and biophysical mechanisms responsible for ET dysfunction. This information is vital to the development of novel treatment therapies that seek to restore normal ET function in patients with OM.